The idea that perhaps there are antigens in endothelial cells, not expressed in lymphocytes, which can cause strong allograft rejection led to the finding, in preliminary experiments, of the endothelial-monocyte (EM) antigens. The EM antigens have been found to be distinct from HLA-A, B, C and DR. They appear to be inherited linked to HLA and are associated with beta 2-microglobulin on the cell surface. Study of these antigens will now focus on their chemical composition, their inheritance in normal and crossover families, their biologic significance and their possible role in allograft rejection. It seems likely that similar antigens exist in other animal species and a detailed plan for performing a series of parallel investigations in inbred strains of mice is also part of this proposal.